Biomedical subjects

A J Smith

Publications and source records attributed to A J Smith.

At least 73 records · Page 4Linked to original sources

PubMed2002

TGF-beta latency-associated peptides (LAPs) in human dentin matrix and pulp.

Transforming growth factor (TGF)-beta s in dentin matrix provide a pool of bioactive molecules, but association with latency-associated peptides (LAPs) may influence their activity. We investigated TGF-beta 1, -beta 2, and -beta 3 LAP expression in sound and carious human teeth. Teeth were fixed and processed immediately following extraction prior to staining with rabbit polyclonal antibodies to the TGF-beta LAPs. A soluble dentin matrix fraction was prepared from dissected human dentin and sequential extraction of pulpal ECM was performed prior to purification. Fractions were Western blotted and probed with the LAP antibodies. All three LAPs were present in odontoblasts, cells of the pulp, and predentin; however, no staining of mineralized dentin matrix was seen. Similar patterns of expression were seen in carious tissue. Expression of TGF-beta LAPs in cells and pulpal matrix of healthy and carious teeth will be important in regulation of TGF-beta activity and may modulate the tissue response to injury.

Dental Caries↗

PubMed2002

Yoghurt biotherapy: contraindicated in immunosuppressed patients?

A fatal case of Lactobacillus rhamnosus septicaemia after prolonged oral vancomycin for recalcitrant Clostridium difficile infection is reported. The patient was immunosuppressed with cyclophosphamide and steroids for Sjögren's syndrome. The administration of Lactobacillus spp as "biotherapy" may be hazardous in such circumstances.

Adult↗

PubMed2002

Psychosocial adjustment and peer competence of siblings of children with Attention-Deficit/Hyperactivity Disorder.

Preliminary data examined the relationships between mothers, their sons with Attention-Deficit/Hyperactivity Disorder (ADHD), and younger siblings. We hypothesized that the conflict between the mother and the son with ADHD would also occur in the relationship between the child with ADHD and the younger sibling. Significant associations were found among ADHD behaviors, family conflict variables, conflict in the relationship between mother and child with ADHD, conflict in the relationship between mother and younger sibling, and conflict in the relationship between the child with ADHD and the younger sibling. Further, significant associations were found between behavior symptoms associated with ADHD and more problematic family relationships. Of particular interest was the finding of an unexpected inverse association between siblings' peer competence and mother-ADHD conflict; specifically, that conflict occurring at home from ADHD accounted for a greater percentage of the variance in peer competence as rated by teachers. Recommendations are made for future research with larger samples, alternative designs, older siblings, and fathers.

Adaptation, Psychological↗

PubMed2001

Gene replacement therapy in the retinal degeneration slow (rds) mouse: the effect on retinal degeneration following partial transduction of the retina.

The retinal degeneration slow (rds or Prph2(Rd2/Rd2)) mouse, a model of recessive retinitis pigmentosa, lacks a functional gene encoding peripherin 2. This membrane glycoprotein is required for the formation of photoreceptor outer segment discs. The striking feature of the rds mouse is the complete failure to develop outer segments. We have previously examined the short-term effect of gene replacement therapy using an adeno-associated (AAV) vector and demonstrated induction of outer segments and improvement of photoreceptor function. Here we have extended our analysis and have demonstrated that the potential for ultrastructural improvement is dependent upon the age at which animals are treated, but the effect of a single injection on photoreceptor ultrastructure may be long-term. However, there was no significant effect on photoreceptor cell loss, irrespective of the date of administration, despite the improvements in morphology and function. Our investigation excluded procedure-related damage, vector toxicity and immune responses as major factors which might counteract the benefits of photoreceptor restoration, but suggested that transgene over-expression is of significance. These findings suggest that successful gene therapy in patients with photoreceptor defects may ultimately depend upon intervention in early stages of disease and upon accurate control of transgene expression.

Animals↗

PubMed2001

Management of needlestick injuries in general dental practice.

The objective of this paper is to advise on the development of practical policies for needlestick injuries in general dental practice. Policies for dealing with occupational exposure to chronic blood borne viruses, namely, hepatitis B, C and HIV are evolving. This article was particularly prompted by recent changes in post exposure prophylaxis for HIV infection. A flow chart is also included which should be of possible use in general dental practice. Needlestick injuries are of increasing concern to healthcare workers. Successful prophylaxis requires careful planning in advance. Whilst all practices should have a policy for sharps injuries, prevention of needlestick injuries remains the best policy.

Blood-Borne Pathogens↗

PubMed2001

Tooth surface pH during drinking of black tea.

OBJECTIVES: To investigate the composition of black tea in terms of its erosive potential. To determine the pH profile at the palatal surface of anterior and posterior sites of the dentition after drinking black tea. METHODS: Tea solution was analysed for its pH and anion composition to provide information on its acid content. A group of ten healthy subjects, aged 21-23 years were monitored for tooth surface pH on the palatal aspects of the maxillary anterior dentition and the maxillary molar dentition after drinking tea using a micro-pH electrode mounted on a vinyl splint. RESULTS: The pH of the tea solution was 4.9 and the major anions detected were oxalate and citrate. Tooth surface pH monitoring indicated that only small decreases in pH of less than 1 pH unit were observed after drinking tea and the minimum mean pH reached was 5.45. Maximum decrease in pH was observed after 20-25 seconds and resting pH levels were restored within approximately 2 minutes after drinking. CONCLUSION: The pH and anion profile of black tea are indicative of low acid composition. The very small pH decreases observed at the tooth surface after drinking tea indicate that it may be safely recommended as a substitute for more acidic drinks as a part of preventive measures for dental erosion.

Adult↗

PubMed2001

p110beta and p110delta phosphatidylinositol 3-kinases up-regulate Fc(epsilon)RI-activated Ca2+ influx by enhancing inositol 1,4,5-trisphosphate production.

Fc(epsilon)RI-induced Ca2+ signaling in mast cells is initiated by activation of cytosolic tyrosine kinases. Here, in vitro phospholipase assays establish that the phosphatidylinositol 3-kinase (PI 3-kinase) lipid product, phosphatidylinositol 3,4,5-triphosphate, further stimulates phospholipase Cgamma2 that has been activated by conformational changes associated with tyrosine phosphorylation or low pH. A microinjection approach is used to directly assess the consequences of inhibiting class IA PI 3-kinases on Ca2+ responses after Fc(epsilon)RI cross-linking in RBL-2H3 cells. Injection of antibodies to the p110beta or p110delta catalytic isoforms of PI 3-kinase, but not antibodies to p110alpha, lengthens the lag time to release of Ca2+ stores and blunts the sustained phase of the calcium response. Ca2+ responses are also inhibited in cells microinjected with recombinant inositol polyphosphate 5-phosphatase I, which degrades inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), or heparin, a competitive inhibitor of the Ins(1,4,5)P3 receptor. This indicates a requirement for Ins(1,4,5)P3 to initiate and sustain Ca2+ responses even when PI 3-kinase is fully active. Antigen-induced cell ruffling, a calcium-independent event, is blocked by injection of p110beta and p110delta antibodies, but not by injection of 5-phosphatase I, heparin, or anti-p110alpha antibodies. These results suggest that the p110beta and p110delta isoforms of PI 3-kinase support Fc(epsilon)RI-induced calcium signaling by modulating Ins(1,4,5)P3 production, not by directly regulating the Ca2+ influx channel.

Animals↗

PubMed2001

Current role of beta-adrenergic blockers in the treatment of chronic congestive heart failure.

Recent findings on the use of beta-adrenergic blockers in patients with congestive heart failure (CHF) are reviewed. CHF is a progressive, debilitating disease that afflicts 4.6 million patients in the United States. Treatment has traditionally consisted of a diuretic, an angiotensin-converting-enzyme (ACE) inhibitor, and digoxin. Despite advances in ACE-inhibitor therapy, the five-year mortality rate remains nearly 50%. Overstimulation of the sympathetic nervous system is believed to contribute to mortality. Beta-blockers have recently been added to the standard of care for patients with New York Heart Association functional class II or III heart failure. Four randomized, double-blind, placebo-controlled clinical trials were recently completed that addressed the benefits of beta-blockers in CHF. The overall mortality rate was reduced 65% by carvedilol, 34% by metoprolol, and 33% by bisoprolol; all these reductions were significant compared with placebo, and the trials were ended early. Bucindolol, however, did not have a significant effect on mortality. These drugs are hepatically metabolized and may require dosage adjustment in hepatically impaired patients. Decompensation of heart failure is another consideration; a beta-blocker should be added only for patients with stable CHF. Dosages must be slowly adjusted to targeted levels. Adverse effects do not differ significantly among beta-blockers. In addition to their effect on mortality, beta-blockers reduce CHF-related morbidity, such as all-cause hospitalization. Carvedilol, metoprolol, and bisoprolol decrease the mortality and morbidity associated with CHF and can be used with limited adverse effects. The choice among these agents does not affect clinical outcomes; bucindolol, however, has proven ineffective.

Drug Compounding↗

PubMed2001

Abnormal bone marrow stroma in mice deficient for nemo-like kinase, Nlk.

The stromal compartment of the bone marrow is composed of various cell types that provide trophic and instructive signals for hematopoiesis. The mesenchymal stem cell is believed to give rise to all major cellular components of the bone marrow microenvironment. Nemo-like kinase, Nlk, is a serine-threonine kinase that connects MAP kinase and Wnt signaling pathways; its in vivo function in mouse is unknown. We have generated mice with a targeted disruption of Nlk and find that the complex phenotype significantly varies with the genetic background. Whereas C57BL/6 mice lacking Nlk die during the third trimester of pregnancy, the 129/Sv background supports survival into adolescence; such mice are growth retarded and suffer from various neurological abnormalities. We show here that the Nlk deficiency syndrome includes aberrant differentiation of bone marrow stromal cells. Varying degrees of morphological abnormality, such as increased numbers of adipocytes, large blood sinuses and absence of bone-lining cells are observed in the bone marrow of mutant mice. Nlk deficient mice thus provide a novel model to study the genetic requirements for bone marrow stromal differentiation.

Animals↗

PubMed2001

Personal formularies. An index of prescribing quality?

OBJECTIVES: (1) To determine the extent to which Australian general practitioners (GPs) restrict the numbers of agents they prescribe within a drug class ('personal formularies'); (2) To assess concordance of these drug choices with standards based on established guidelines or recognised good prescribing practices; (3) To assess the potential of these measures as indicators of the quality of prescribing. METHODS: Australian Health Insurance Commission (HIC) prescription data (1994 1997) for around 15,400 GPs providing 1500 or more Medicare services per year were analysed. Measures of an individual GP's use of a personal formulary (determined by number of agents) and concordance with prescribing criteria based on specified drugs for five classes of commonly prescribed drugs were derived. RESULTS: Non-steroidal anti-inflammatory drugs (NSAIDs): GP concordance was higher with a non-specified personal formulary (any five NSAIDs) than with a list of specified drugs (five NSAIDs of 'low' or 'medium' risk of gastrointestinal toxicity), and concordance with both increased over time. In 1997, around 70% of GPs used five or fewer NSAIDs for 90% of their prescribing; 47% of GPs had 90% of prescribing from five selected agents. Angiotensin converting enzyme inhibitors/angiotensin-II receptor antagonists: The introduction of new agents appeared to increase the size of the GPs' personal formularies, and concordance with defined standards decreased over time. Antibacterial agents: Concordance with a specified drug standard (nine drugs listed in the Australian Antibiotic Guidelines) increased substantially over time but was largely due to increased prescribing of two heavily promoted drugs. Beta-blocking agents: Over time, GPs restricted most prescribing to two agents, atenolol and metoprolol. Calcium channel blockers: GPs did not appear to restrict prescribing of these drugs; most GPs prescribed all five agents available. CONCLUSIONS: Australian GPs use 'personal formularies'. Formulary size varies with the drug class, can change over time as new agents become available, and its contents can be influenced by promotional activities. Prescribing standards based on numbers of drugs used may not always reflect rational prescribing choices. Criteria based on specified drugs provide more rigorous prescribing standards, but may give a misleading picture of prescribing quality in the absence of information on patients and the indications for treatment. Personal formulary measures are potentially useful prescribing indicators but need to be carefully defined and interpreted. GPs should be encouraged to identify their personal formularies and review the drugs included in them.

Australia↗

PubMed2001

The bio-availability of fluoride from black tea.

OBJECTIVES: To investigate the oral retention of fluoride from tea and its association with the tooth surface and acquired pellicle. METHODS: Oral retention of fluoride after rinsing in vivo was assessed from expectorated samples with an ion specific electrode methodology. Interaction of fluoride with the tooth surface and acquired pellicle was examined in situ with enamel blocks mounted on partial removable appliances. In vitro models were used to examine fluoride binding to enamel particles. RESULTS: Thirty four percent of the fluoride was retained in the oral cavity after rinsing with tea. Differences in retention at the tooth surface in the presence and absence of an acquired pellicle were not statistically significant at incisor or molar sites. Fluoride from tea showed strong binding to enamel particles, which was only partially dissociated by solutions of ionic strength considerably greater than that of saliva. Binding studies demonstrated strong avidity of enamel for tea and salivary pellicle components. CONCLUSIONS: This study has demonstrated that tea can provide an effective vehicle for fluoride delivery to the oral cavity where it may interact with the oral tissues and their surface integuments. This may lead to local topical effects of the ingested fluoride as well as systemic effects following oral and gastro-intestinal absorption.

Adult↗

PubMed2001

The effect of cavity restoration variables on odontoblast cell numbers and dental repair.

OBJECTIVES: Dentinal repair following cavity restoration is dependent on several parameters including the numbers of surviving odontoblasts. The purpose of this study was to examine the effects of cavity cutting and restoration treatments on post-operative odontoblast numbers. METHODS: 353 Standardised non-exposed rectangular Class V cavities, were cut into the buccal dentin of intact 1st or 2nd premolar teeth of 165 patients, aged between nine and 25 years of age. Composite cavity restorations with various etching treatments were compared with resin-modified glass ionomer cements, enamel bonding resins, as well as polycarboxylate, calcium hydroxide, and zinc oxide eugenol materials. Following tooth extraction (20-381 days) for orthodontic reasons, the area of the reactionary dentine and the area of the odontoblasts was measured histomorphometrically. RESULTS: Odontoblast numbers and dentine repair activity were found to be influenced more by cavity restoration variables, than the choice of cavity filling materials or patient factors. The most important cavity preparation variable was the cavity remaining dentine thickness (RDT); below 0.25mm the numbers of odontoblasts decreased by 23%, and minimal reactionary dentine repair was observed. CONCLUSIONS: Odontoblast injury increased as the cavity RDT decreased. In rank order of maintaining odontoblast numbers beneath restored cavities with a RDT below 0.5mm, and using calcium hydroxide for comparison; calcium hydroxide (100%), polycarboxylate (82.4%), zinc oxide eugenol (81.3%), composite (75.5%), enamel bonding resin (49.5%) and RMGIC (42.8%). The vitality and dentine repair capacity of the pulp is dependent on odontoblast survival. Variations in the extent of odontoblast injury caused during operative procedures, may be the major underlying reason for the success or failure of restorative treatments.

Adolescent↗

PubMed2001

Transdentinal stimulation of reactionary dentinogenesis in ferrets by dentine matrix components.

OBJECTIVES: Trans-dentinal stimulation of reactionary dentinogenesis may be mediated through cellular signalling by bio-active components released from the dentine matrix during injury. Understanding of these processes will be important to guide dentinal repair activity following restorative surgery. The purpose of this study was to investigate the effects of implanting isolated dentine matrix proteins within cavity preparations on dentinal repair activity and odontoblast survival using a controlled experimental animal model. METHODS: Forty-five ferret canine teeth each had a standardised non-exposed cylindrical Class V cavity cut into the buccal dentine. Ten cavities were restored with zinc oxide eugenol, as a control. Two different lyophilised preparations of dentine matrix components were implanted on the axial floor of the remaining 35 cavities prior to filling with zinc oxide eugenol. After post-operative periods of 2, 7, 14, 28, and 90 days, the teeth were extracted and examined histomorphometrically and the data analysed statistically by analysis of variance tests. RESULTS: The odontoblasts beneath the restored cavities responded to the presence of the two dentine matrix preparations by increasing the mean area of reactionary dentine secreted by 433 and 578%, and the numbers of odontoblasts remained stable. CONCLUSION: Dentine matrix components can stimulate reactionary dentinogenesis in non-exposed cavity preparations. It will now be important to identify how this may be harnessed as a part of routine restorative surgery to optimise treatment outcomes with a biological basis.

Analysis of Variance↗

PubMed2001

Olanzapine overdose.

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Antipsychotic Agents↗

PubMed2001

Blood pressure measurement in volunteers with and without padding between the cuff and the skin.

Automated non-invasive arterial blood pressure measurements are made frequently during anaesthesia. Conscious patients often find the measurement uncomfortable. The tissues under the cuff can suffer trauma such as skin creasing, blistering, petechial haemorrhages and even nerve damage. We placed soft padding between the blood pressure measurement cuff and the skin of the upper arm of 140 healthy volunteers, and compared cuff-related skin trauma and arterial blood pressure measurements with and without the padding. Padding was associated with a significant reduction in the frequency and intensity of skin trauma (p < 0.0001). There was no significant overall effect of the presence of padding on arterial blood pressure readings. We conclude that the benefit of padding outweighs any compromise to the reliability of arterial blood pressure measurement.

Adult↗

PubMed2001

Vegetarian children and dental erosion.

BACKGROUND: There have been recent changes in teenage lifestyle and diet. The increasing consumption of soft drinks and foods containing significant acidic components may play a role in the development of dental erosion. OBJECTIVE: The aims of this investigation were firstly to assess the prevalence of vegetarian children in a cluster random sample of 14-year-old children in Birmingham, United Kingdom. Secondly, to determine the prevalence of dental erosion in these children, and thirdly, to see if there were any differences between vegetarian and non-vegetarian children in the prevalence of dental erosion and dietary intake. DESIGN: A cluster random sample of 418 14-year-old children (209 males and 209 females) were examined from 12 different schools in Birmingham, United Kingdom; a dietary questionnaire was completed and the levels of tooth wear were recorded using a modification of the (TWI) index. All data were analysed using SPSS with t-test and Chi-square analysis. Significance was accepted at the P < 0.05 level. RESULTS: The results showed that 10% of the children were vegetarian; 52% of them had low dental erosion and 48% moderate dental erosion. Statistically there were no significant differences between vegetarian and non-vegetarian children in the prevalence of erosion; however, there were significant differences in some food and drink consumption. CONCLUSIONS: It was concluded that dental erosion is common in teenage children, but there were no significant differences in prevalence between vegetarian and non-vegetarian children.

Adolescent↗

PubMed2001

Investigation of mineral waters and soft drinks in relation to dental erosion.

A range of still and sparkling mineral waters were assessed for their erosive potential together with comparator soft drinks using in vitro dissolution assays with extracted human teeth and powdered hydroxyapatite. Dissolution levels with all of the mineral waters were very low and for several still waters were undetectable. Sparkling mineral waters showed slightly greater dissolution than still waters, but levels remained low and were of the order of one hundred times less than the comparator soft drinks. De-gassing of a sparkling mineral water reduced its dissolution, but the total levels were still relatively low suggesting that carbonation of drinks may not be an important factor per se in respect of erosive potential. The complex and heterogeneous mineral compositions of mineral waters could influence the dissolution equilibrium of apatite in enamel and controlled addition of several ions to ultrapure deionized water was investigated. Calcium ions led to the greatest reduction in hydroxyapatite dissolution, but their effects were moderated by other ions including magnesium and sulphate. Thus, mineral waters appear to offer a safe alternative to more erosive acidic beverages and their complex mineral ion compositions may positively influence any dissolution processes at the tooth surface.

Apatites↗

PubMed2001

Artificial saliva substitutes and mineral dissolution.

The erosive potentials of a number of commercially available artificial saliva substitutes have been investigated using an in vitro hydroxyapatite powder dissolution assay. Most of the saliva substitutes examined did not show any appreciable erosive potential, although one product resulted in greater mineral dissolution levels. There appeared to be little correlation between pH and mineral dissolution levels for the different saliva substitutes examined. Whilst saliva substitutes may be of assistance in maintaining some physiological function in patients with impaired salivary flow, it is important to choose a product with low erosive potential where the natural dentition is present.

Aerosols↗